QSAR models for antioxidant activity of new coumarin derivatives.

This study presents 37 new antioxidant coumarin derivatives and strategies for structural modification to improve their antioxidant activities, the main ferric-reducing antioxidant power (FRAP) assay used to evaluate their antioxidant properties and the generation of validated quantitative structure-activity (antioxidant activity) relationship (QSAR) models. In an attempt to generate QSAR models, structures of all coumarin derivatives in the data set were fully optimized by semi-empirical PM6 method using SPARTAN 10 software. Descriptors were calculated by DRAGON 6.0 software. Multiple linear regression (MLR) models were developed with different training/test set combinations using QSARINS 2.2.1 software. Robustness, reliability and predictive power of the models were tested by internal and external validations. Applicability domain of the best two-descriptor model (nTR = 30; r(2) = 0.924; RMSETR = 0.213; nTEST = 7; r(2)ext = 0.887; RMSEext = 0.255; CCCext = 0.939) was determined. Descriptors appeared in the model revealed that complexity, H-bond donor and lipophilic character are important parameters in describing the antioxidant activity. Apart from the compounds in the data set, we also designed 31 new antioxidant coumarin derivatives and predicted their antioxidant activity using the best two-descriptor model. Most of these compounds are promising antioxidants.

Dysnatremia on intensive care unit admission is a stronger risk factor when associated with organ dysfunction.

AIM: Dysnatremia present at the time of intensive care unit (ICU) admission is associated with mortality. In this study, we investigated the epidemiology of dysnatremia present on ICU admission and the impact of organ dysfunction on the association between dysnatremia and mortality. We hypothesized that dysnatremia comorbid with organ dysfunction is associated with higher risk of mortality. METHODS: This retrospective study was conducted on all patients admitted to the International Hospital General ICU in Istanbul over a period of 6 years (2006-2011). Patients were classified, according to the most abnormal serum sodium values measured within 24 hours after ICU admission, into 7 groups as follows: normonatremia (135≤Na≤145 mmol/L), borderline hyponatremia (130≤Na<135 mmol/L), mild hyponatremia (125≤Na<130 mmol/L), severe hyponatremia (Na <125 mmol/L), borderline hypernatremia (145155 mmol/L). RESULTS: The total admitting patient were 1657. A total of 1060 patients' data were analyzed in this study. Sodium levels were normal in 637 (60.1%), hyponatremic in 367 (34.6%) and hypernatremic in 56 (5.3%) patients. Multivariate analysis showed that only SAPS II was associated with increased mortality (OR, 1.05 [95% confidence interval, 1.02-1.09]). The odds ratio (95% CI) of dysnatremia (Na <125 mmol/L and >150 mmol/L) for mortality was 4.37 (2.29-8.36) in patients with organ dysfunction (number of dysfunctional organs ≥1) (P<0.001). CONCLUSION: Below 125 and above 150 mmol/L sodium levels at ICU admission are risk factors for higher mortality rates in patients with comorbid organ dysfunction. The effect of dysnatremia on mortality is observed when organ dysfunction is present.

Production of cellulase by immobilized whole cells of Haloarcula.

Halophilic Archaea are adapted to a life in the extreme conditions and some of them are capable of growth on cellulosic waste as carbon and energy source by producing cellulase enzyme. The production of cellulase using free and immobilized cells of halophilic archaeal strain Haloarcula 2TK2 isolated from Tuzkoy Salt Mine and capable of producing cellulose was studied. The cells were cultured in a liquid medium containing 2.5 M NaCl to obtain the maximum cellulase activity and immobilized on agarose or polyacrylamide or alginate. Optimal salt dependence of free and immobilized cells of Haloarcula 2TK2 was established and the effects of pH and temperature were investigated. Immobilization to Na-alginate enhanced the enzymatic activity of the haloarchaeal cells when compared to free cells and other polymeric supports. From the results obtained it is reasonable to infer that decomposition of plant polymers into simpler end products does occur at high salinities and cellulase producing haloarchael cells may be potentially utilized for the treatment of hypersaline waste water to remove cellulose.

Antistreptolysin O, rheumatoid factor and C-reactive protein determination in patients with recurrent oral ulcer.

Recurrent oral ulcer (ROU) is a common disease whose the etiologic factors have not yet been identified. Although the autoimmune mechanism due to streptococcal antigens may be involved in this disease, serum immunoglobulins are reported to be higher than normal controls in various phases of ROU. Oral ulcers are one of the criteria in the diagnosis of some systemic diseases such as Wegener's granulomatosis, Behçet's syndrome, suppurative arthritis, Reiter's syndrome and neutropenias. Any patient with recurring oral ulcers should be evaluated medically for the possible presence or future development of serious systemic diseases. In this study of the 58% of the ROU patients who had positive ASO values, only one female patient had a moderate increase: ++ASO(= 400 IU), the rest had a slight increase: +ASO(= 200 IU). In the control group only 3 female subjects had +ASO (= 200 IU). The aim of this study was to determine whether there is any relationship between ROU and rheumatoid arthritis. Patients with ROU were examined for antistreptolysin O, rheumatoid factor and C-reactive protein and compared to healthy controls.

Lipid composition of nipple discharges of women with galactorrhea.

The biochemical nature of nipple discharge, including galactorrhea, and the physiology of lactation in patients with nipple discharge have not been studied extensively. Studies of the composition of nipple discharges may provide further insight into the complex processes involved in their secretion. In this study we compared the lipid composition of nipple discharges from patients with galactorrhea with that of human colostrum. The diagnosis of galactorrhea was confirmed by the presence of casein, detected by the anti-casein radial immunodiffusion test. Triglyceride, cholesterol and phospholipid levels in the nipple discharge samples were quite high compared with the colostrum samples. The proportion of 6:0 and 22:1 fatty acids was lower in the discharge samples and the proportion of 18:2 and 20:4 fatty acids was higher. Levels of phospholipid and neutral lipids, determined by quantitative densitometry in situ after separation by thin layer chromatography, also varied between discharge and colostrum, with a higher level of free fatty acids and triglyceride fractions in the nipple discharge. The lipoprotein electrophoretic bands of the nipple discharge samples resembled serum lipoprotein bands while colostrum samples gave no bands on electrophoresis.

Erythrocyte membrane enzymes in sickle cell anemia. 2. Acetylcholinesterase and ATPase activities.

The activity level of acetylcholinesterase in the erythrocytes of 32 patients homozygous for sickle cell anemia was determined and compared with that of normal AA controls as well as with that of AS individuals. Acetylcholinesterase activity was markedly higher in erythrocyte membrane from SS individuals than in those from AS individuals or AA controls. Additionally, ATPase activities were also significantly higher in sickle cell erythrocytes as compared to normal cells. These higher values of acetylcholinesterase and ATPase activities in SS erythrocytes may be explained as a consequence of the abnormally high cation levels in sickle cell erythrocytes.

Reactive oxygen production against malaria--a potential cancer risk factor.

In response to malaria infection, phagocytes, such as macro-phages and neutrophils, produce superoxide and thence the other reactive oxygen species (ROS) with which to kill the parasites. Excess ROS is normally eliminated by the body's natural scavenger molecules; however, in the event of a vast excess of ROS, as may be the case in acute as well as chronic malaria patients, the natural scavengers may be overwhelmed. We hypothesize that unscavenged ROS in malaria patients causes DNA damage in normal host cells which, if unrepaired or incorrectly repaired, could result in oncogene activation and eventually lead to cancer. An epidemiologic study may be warranted in malaria-endemic regions to investigate the possible relationship between malaria infection and cancer risk.

Acetylation polymorphism and leprosy.

The sulfones are the drug of choice in the treatment of leprosy, with dapsone as the clear favorite. The major route for dapsone metabolism leading to its inactivation and excretion is via acetylation by hepatic N-acetyl transferase (NAT), as is the case with isoniazid (INH) and sulfamethazine (SMZ). The enzyme is known to exhibit genetic polymorphism. The object of the present study is mainly to determine the incidence of acetylator phenotype in a population of leprosy patients with a view to evaluating the degree of association, if any, between phenotype and the disease. Obviously a knowledge of the incidence of the phenotypes may provide a valuable contribution to the institution of more rational and successful therapy. In the normal or control subjects, as well as in the leprosy patients, the frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum samples are bimodal, and this indicates the existence of a genetic polymorphism. Based on the bimodality, individuals were classified as either "rapid" or "slow" acetylators, and the incidence of the slow acetylator phenotype of about 51% was observed in the leprosy population. This gives a relatively high incidence of the allele controlling the slow acetylator (q = 0.73). Although there is evidence that the mean percentage of SMZ acetylated in leprosy patients of the slow acetylator phenotype is significantly higher than that observed for the same phenotype in the controls (t = 4.86, P less than 0.02), statistical analyses show that there is no association between the slow acetylator phenotype and the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oxygen free radical scavengers on the membrane myoinositol dehydrogenase of Bacillus pumilus strain 5.

Micromolar amounts of superoxide dismutase (SOD) or parabenzoquinone (PBQ) inhibit the membrane-bound myoinositol dehydrogenase of Bacillus pumilus strain 5 in the mode of this enzyme transferring electrons to 2,6-dichlorophenol indophenol (DCPIP). The inhibition trends are similar to those reported earlier by us for the inhibition by mannitol and benzoate. We postulate that the transfer of electrons from the enzyme to DCPIP involves in its rate-limiting step, a catalytic intermediate in the nature of superoxide (O2-) and/or hydroyl free radical (OH.). Scavenging of any one or both of these radicals, therefore, inhibits the electron transfer reaction. PBQ serves as an electron sink in the reaction preventing the reduction of DCPIP.

An oxytocic extractive from a West African cucurbit. Studies on west African medicinal plants. 8.

PIP: In south-east Nigeria the plant Mormordica cabrei, of the Cucurbitac eae family, is believed to be an abortifacient. A crude methanol-soluble extractive of the fruit, branches, and roots of the plant caused an intense spasm when administered to pregnant and non-pregnant uterine tissue, in vitro. The physiologically active principle appears to be cucurbit glycosides.^ieng